A general analytical methodolgoic approach is described for the development of new regulatory methods for drug residue measurements in food animal products. this methodology is based on the use of solid phase extraction (SPE) columns and tandem mass spectrometric (MS/MS) technologies. The use of SPE colums offers the capability of isolating one or a group of drugs in a single analysis, thus making the extraction method general in nature yet specific for a given application. This SPE technology reduces the time, materials and labor necessary for conducting drug isolation and is amenable to automation. Tandem mass spectrometry (MS/MS) is proposed as a versatile method for conducting sensitive and specific drug screening, quantitation and confirmation. We will examine the use of direct exposure probe (DEP)-, gas chromatographic-, and high pressure liquid chromatographic/MS/MS techniques for conducting screening, quantitation and confirmation of indiviual drugs nad groups of drugs, isolated from spiked tissues, in a single analysis. The availability of this methodologic approach could simplify the development of new regulatory methods by drug sponsors, while providing techiques that are generally applicable to the monitoring of drug residues in food animal products.